Recently, 3, 4-methylenedioxymethamphetamine (MDMA) became popular as a recreational substance of abuse and was subsequently placed into Schedule I of the Controlled Substances Act. Although MDMA is structurally related to the hallucinogenic amphetamines, it may possess novel psychoactive properties. In view of MDMA's recreational popularity, and its potentially novel pharmacological properties, it is important to understand how MDMA works. This proposal describes a comprehensive program to: 1. study the behavioral properties of MDMA and related compounds, in the drug discrimination paradigm in rats, and to compare MDMA with other, known psychoactive phenethylamine derivatives in this model, 2. to study the biochemical pharmacology of MDMA and related compounds for an effect on monoamines neurotransmitter function in rat brain synaptosomes, with particular emphasis on comparison of neurotransmitter uptake and release mechanisms, 3. to measure the binding affinity of 3H-labeled enantiomers of MDMA and its alpha-ethyl congener MBDB, and to generate displacement curves with a variety of neurochemicals to fully characterize MDMA binding sites, and 4. to synthesize a series of structurally-related compounds, and to assay their pharmacology. These studies will provide further elucidation of the mechanism of action of MDMA and related compounds, and will define the structure-activity relationships wherein compounds with an MDMA-like effect are likely to be found.